We investigated the responses of patients with malignant histiocytosis (MH) to the treatment of epotoside-based regimen. Of 11 evaluable cases, 9 (81.8%) achieved complete remission and 1 partial remission. 7 complete remission cases (77.7%) received only one therapeutic course. The side effects were mild and well-tolerated. We conclude that etoposide-containing regimen is highly effective and can be used as first-line treatment for MH and is worthy of further study.